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bioRxiv · 10.64898/2026.06.28.735116

Protocol for standardized minimally invasive mouse models of bisphosphonate-related and radiation-induced jaw osteonecrosis

Ding, Z.·Zhang, J.·Liu, H.·Chandra, A.·Risbud, M. V.·Kusumbe, A. P.·Chen, J.
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Abstract

This protocol describes a standardized and reproducible minimally invasive approach for establishing mouse models of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and osteoradionecrosis of the jaw (ORNJ). The method combines a unified low-trauma oral surgical procedure with disease-specific injury induction strategies to generate robust and clinically relevant models of jaw osteonecrosis. For BRONJ, systemic zoledronic acid administration is coupled with mandibular first molar extraction using tape-assisted mouth opening and customized bent micro-forceps, minimizing soft tissue damage and reducing procedural variability. For ORNJ, a customized lead-shielding platform enables precise, noninvasive mandible-targeted irradiation, producing reproducible bone injury while limiting off-target radiation exposure. Together, these complementary models provide a consistent and minimally invasive framework for investigating jaw osteonecrosis arising from distinct etiologies. The protocol supports comprehensive downstream analyses, including micro-computed tomography, histology, and immunofluorescence, and facilitates mechanistic studies of disease pathogenesis, bone regeneration, and therapeutic intervention.

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Ding, Z., Zhang, J., Liu, H., Chandra, A., Risbud, M. V., Kusumbe, A. P., Chen, J.. 2026-07-03. Protocol for standardized minimally invasive mouse models of bisphosphonate-related and radiation-induced jaw osteonecrosis. https://doi.org/10.64898/2026.06.28.735116

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